JP2006241172A - Preventive or remedy for endometriosis - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a drug effective for prevention and therapy of endometriosis and hysteromyoma. <P>SOLUTION: The drug effective for prevention and therapy of endometriosis and hysteromyoma comprises a macrolide antibiotic as an effective ingredient. The endometriosis can effectively be treated by this preventive or therapeutic agent. Since the patients with endometriosis rapidly increase and become main causes of menstrual colic and infertility, this invention can be thought to largely contribute in the fields of the prevention and treatment for infertility and menstrual colic. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a preventive or therapeutic agent for endometriosis and uterine fibroids.

  Endometriosis is a disease in which endometrium or intima-like tissue expands ectopically at sites other than the inner surface of the uterine cavity. The cause of endometriosis is unknown, and treatments such as surgical removal of adhesions, administration of hormones, administration of analgesics, etc. are performed, but these are all symptomatic treatments and are fundamental treatments There is no way.

  Uterine fibroids are benign tumors in the muscles of the uterus that cause abnormal menstrual flow and abnormal bleeding. In addition, when the myoma is large, the surrounding organs are compressed, and it becomes easy to cause hyperemia in the pelvis, low back pain and traction pain. There is no treatment for uterine fibroids other than surgery, and surgery is based on total hysterectomy. There is no drug treatment for uterine fibroids.

  An object of the present invention is to provide a drug effective for the prevention and treatment of endometriosis or uterine fibroids.

  As a result of intensive studies, the present inventors have found that macrolide antibiotics have preventive and therapeutic effects on endometriosis and uterine fibroids, and have completed the present invention.

  That is, the present invention provides a preventive or therapeutic agent for endometriosis or uterine fibroids containing a macrolide antibiotic as an active ingredient. The present invention also provides the use of a macrolide antibiotic for the manufacture of a prophylactic or therapeutic agent for endometriosis or uterine fibroids. Furthermore, the present invention includes administering to a patient with endometriosis or uterine fibroid an amount of macrolide antibiotic effective to prevent or treat endometriosis or uterine fibroid, A method for preventing or treating uterine fibroids is provided.

  The present invention provides for the first time an agent effective for the prevention and treatment of endometriosis that can treat endometriosis. Endometriosis is one of the main causes of menstrual pain and infertility due to the rapid increase in the number of patients. Therefore, the present invention greatly contributes to the fields of fertility treatment and menstrual pain treatment and prevention. it is conceivable that. The macrolide welfare substance is also effective for the prevention and treatment of uterine fibroids that show pathological findings similar to endometriosis.

  As described above, the preventive or therapeutic agent for endometriosis of the present invention is effective for both prevention and treatment of endometriosis, and contains a macrolide antibiotic as an active ingredient. The macrolide antibiotic means a group of antibiotics having a 12 to 16 membered lactone ring (the number of atoms constituting the ring is 12 to 16) and a neutral or amino sugar. Examples of macrolide antibiotics that can be used in the present invention include clarithromycin, roxithromycin, azithromycin, erythromycin, josamycin, leucomycin group, spiramycin group, carbomycin group, silamycin group, tylosin, angolamycin, kitasamycin Acetyl spiramycin, midecamycin, roxistamycin, oleandomycin, myrosamycin and maridomycin and their hydrated salts, non-toxic salts and derivatives, but are not limited thereto. The term “derivative” as used herein means that the basic skeleton consisting of a lactone ring and a sugar is the same as the original compound, and the substituent bonded to the lactone ring and / or sugar is changed, and has an antibiotic action These derivatives can also be used as long as they have them. Non-toxic salts include hydrochloride, sulfate, tartrate, citrate and the like, but are not limited thereto. As the macrolide antibiotic, those having a lactone ring of 14-membered ring or 15-membered ring are preferable, and those having two sugars bonded thereto are preferable. In particular, clarithromycin, roxithromycin and azithromycin are preferred.

  The preventive or therapeutic agent for endometriosis of the present invention can be administered by any administration method including oral administration and parenteral administration such as intravenous administration, subcutaneous administration, intramuscular administration, and enteral administration. Oral administration is convenient and preferred. The dose is appropriately set according to the degree of symptoms of the patient and the type of macrolide antibiotic used, but is usually about 300 mg to 500 mg of macrolide antibiotic per day for adults. It is effective at a dose that can be used to treat the disease.

  Endometriosis is an ectopic appearance of endometrium or intimal-like tissue in the myometrium, which is a form of endometriosis and is included in endometriosis (“ Surgical pathology ", p713-715, published by Bunkodo," clinical histopathology ", p661, published by Kyorin Shoin.

  The inventor of the present application also conducted extensive research on the findings of uterine fibroids. As a result, the presence of mastocytosis and degranulation were observed pathologically in uterine fibroids. Confirmed with. Therefore, macrolide antibiotics are effective for the treatment and prevention of uterine fibroids as well as endometriosis.

  In addition, about the macrolide antibiotic used for treatment or prevention of a uterine fibroid, its administration route, dosage, etc., the above-mentioned description about endometriosis is applicable as it is.

  For the formulation, any formulation method commonly used in the field of pharmaceuticals can be employed. For example, it can be granulated with additives such as polyoxyethylene sorbitan fatty acid ester, propylene glycol or sodium lauryl sulfate, and compressed into tablets, but is not limited thereto. Examples of preparations include, for example, mixing 50 mg of clarithromycin and 34 mg of polyoxyethylene sorbitan fatty acid ester, granulating and tableting into tablets, but of course limited to this is not.

  Since macrolide antibiotics have already been used as therapeutic agents for various infectious diseases, the safety required for pharmaceuticals has been confirmed.

  Hereinafter, the present invention will be described more specifically based on examples. However, the present invention is not limited to the following examples.

Example 1 Treatment effect of endometriosis with clarithromycin Endometriosis model rats were prepared by the method described in Michael W. Vernon et al., FERTILITY AND STERILITY, Vol. 44, No. 5, November 1985. did. That is, endometriosis model rats were prepared as follows. 8 weeks old Sprague-Dawley rats (female) were acclimated for 12 hours in a light and dark environment for 2 weeks, and then the right uterine horn was removed under general anesthesia with sevoflurane and ketamine hydrochloride, 5 x 5 mm uterine tissue A piece was made and autografted with the endometrial surface facing the peritoneum.

  24 hours after the preparation of endometriosis model rats, commercially available clarithromycin tablets (trade name “Claris Tablets 50 for children” manufactured by Taisho Pharmaceutical Co., Ltd.) are orally administered to endometriosis model rats over 3 days. did. The dose was 10 mg / kg per day in terms of clarithromycin. Controls did not receive clarithromycin. Seven days after the model creation, which is the peak of the model lesion, the peritoneal tissue including the graft was excised to the abdominal muscle, and the lesion material was collected. From these materials, optical microscope specimens (hematoxylin / eosin staining, toluidine blue staining) and electron microscope specimens (uranium / lead heavy staining) were prepared. The extent of the proliferative lesion was observed.

  As a result, mast cell infiltration and stromal proliferative lesions were observed in the control group, but mast cell infiltration was not observed in the clarithromycin administration group, and the degree of stromal proliferative lesions was also clearly suppressed. It was.

Example 2 Therapeutic effect of endometriosis with roxithromycin The same operation as in Example 1 except that roxithromycin (trade name “Lurid Tablet 150”, manufactured by Eisai Co., Ltd.) was used instead of clarithromycin. Went. The dose was 6 mg / kg per day in terms of roxithromycin. As a result, mast cell infiltration and stromal proliferative lesions were observed in the control group, but mast cell infiltration was not observed in the roxithromycin administration group, and the degree of stromal proliferative lesions was also clearly suppressed. It was.

Example 3 Treatment effect of endometriosis with azithromycin The same operation as in Example 1 was performed except that azithromycin (trade name “Zithromac Tablets 250 mg”, manufactured by Pfizer Pharmaceutical Co., Ltd.) was used instead of clarithromycin. It was. The dose was 10 mg / kg per day in terms of azithromycin. As a result, mast cell infiltration and stromal proliferative lesions were observed in the control group, but mast cell infiltration was not observed in the azithromycin-administered group, and the degree of stromal proliferative lesions was clearly suppressed. .

Claims (3)

  An agent for preventing or treating endometriosis or uterine fibroids containing a macrolide antibiotic as an active ingredient.   The prophylactic or therapeutic agent according to claim 1, wherein the macrolide antibiotic is clarithromycin, roxithromycin or azithromycin. The prophylactic or therapeutic agent according to claim 1 or 2, which is a prophylactic or therapeutic agent for endometriosis.